Polycomb Repressive Complex 2: Emerging Roles in the Central Nervous System

Abstract

The polycomb repressive complex 2 (PRC2) is responsible for catalyzing both di- and trimethylation of histone H3 at lysine 27 (H3K27me2/3). The subunits of PRC2 are widely expressed in the central nervous system (CNS). PRC2 as well as H3K27me2/3, play distinct roles in neuronal identity, proliferation and differentiation of neural stem/progenitor cells, neuronal morphology, and gliogenesis. Mutations or dysregulations of PRC2 subunits often cause neurological diseases. Therefore, PRC2 might represent a common target of different pathological processes that drive neurodegenerative diseases. A better understanding of the intricate and complex regulatory networks mediated by PRC2 in CNS will help to develop new therapeutic approaches and to generate specific brain cell types for treating neurological diseases.

Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

“…The PRC2 protein complex is composed of three core component proteins: SUZ12, EED, and either EZH1or EZH12, which along with RBBP4 or RBBP7 forms distinct subcomplexes by associating with different interaction partners. It is highly conserved and was originally discovered in Drosophila studies as a suppressor of Hox genes 53,54 . It is well known that PRC2 mediates the methylation of Histone 3 lysine 27 (H3K27).…”

The Dynamic Partnership of Polycomb and Trithorax in Brain Development and Diseases

“…Members of PRC2 have been implicated in numerous roles including, but not limited to: neuronal identity, proliferation, differentiation and neuronal morphology [99]. Here, we discuss the roles of the core proteins (EZH2, EED, SUZ12 and RBAP46/48) and their unique involvement in neurogenesis.…”

The control of polycomb repressive complexes by long noncoding RNAs

“…As the embryo differentiates, the overall levels of the PRCs decrease, concomitant with changes in the composition of PRC accessory subunits (Aloia et al, 2013;Kloet et al, 2016;Kuzmichev et al, 2005; J. R. Yu et al, 2019). Nevertheless, the PRCs play critical roles in many lineages, including adult stem cell populations as well as in more differentiated cell types (Akerberg & Pu, 2019;Brand et al, 2019;Desai & Pethe, 2020;Di Carlo et al, 2019;P. P. Liu et al, 2018;Vidal & Starowicz, 2017; J. R. Yu et al, 2019).…”

“…As the embryo differentiates, the overall levels of the PRCs decrease, concomitant with changes in the composition of PRC accessory subunits (Aloia et al, 2013; Kloet et al, 2016; Kuzmichev et al, 2005; J. R. Yu et al, 2019). Nevertheless, the PRCs play critical roles in many lineages, including adult stem cell populations as well as in more differentiated cell types (Akerberg & Pu, 2019; Brand et al, 2019; Desai & Pethe, 2020; Di Carlo et al, 2019; P. P. Liu et al, 2018; Vidal & Starowicz, 2017; J. R. Yu et al, 2019). Accordingly, mutation or misexpression of the PRCs and their accessory factors is associated with many forms of disease, including cancer, overgrowth syndromes, malignant hematological disorders, and forms of intellectual disability (Chan & Morey, 2019; Comet et al, 2016; Cyrus et al, 2019; Deevy & Bracken, 2019; Di Carlo et al, 2019; Isshiki & Iwama, 2018; Poynter & Kadoch, 2016; Srivastava et al, 2017; Vidal & Starowicz, 2017).…”